Boceprevir dosing for late responders and null responders: The role of bridging data between treatment-naïve and -experienced subjects

The Utility of Modeling and Simulation in Drug Development and Regulatory Review

“…Three case studies are highlighted below to illustrate the application of pharmacometric analyses to address two major challenges: dose optimization and extrapolation of therapeutic effect to unstudied populations. [13][14][15][16][17][18] The models applied in our evaluation are listed in Table 2.…”

Direct‐acting antiviral drugs for the treatment of chronic hepatitis C virus infection: Interferon free is now

“…Among persons with genotype 1 chronic HCV infection who are treated with PEG‐IFN/RBV, SVR is achieved in 69%, 33%, and 27% of Caucasians who have the CC, CT, and TT genotypes, respectively; among Black patients, SVR rates were 48%, 15%, and 13% for CC, CT, and TT genotypes, respectively. The predictive value of IL28B genotype testing for SVR for PEG‐IFN/RBV‐based regimens is superior to that of the pretreatment HCV RNA level, fibrosis stage, age, and sex, and is higher for HCV genotype 1 virus than for genotypes 2 and 3 viruses …”

“…The predictive value of IL28B genotype testing for SVR for PEG-IFN/RBV-based regimens is superior to that of the pretreatment HCV RNA level, fibrosis stage, age, and sex, and is higher for HCV genotype 1 virus than for genotypes 2 and 3 viruses. 31,32…”

FDA bridging analyses confirmed in clinical trial

“…2 To address this, bridging analyses were conducted based on the concept that a patient's virologic response to PR remains relatively unchanged with subsequent treatment courses. 2 These analyses predicted a sustained virologic response (SVR) rate of 28-30% in treatment-na€ ıve patients with <0.5 log 10 hepatitis C virus (HCV) RNA decline at week 4 (poorly interferon responsive). Based on these analyses, the Food and Drug Administration (FDA) recommended the use of boceprevir in combination with PR for all patients who have failed previous PR therapy.…”

“…Based on these analyses, the Food and Drug Administration (FDA) recommended the use of boceprevir in combination with PR for all patients who have failed previous PR therapy. 2 However, to ensure that the FDA recommendations were scientifically sound, the data from the PROVIDE study postmarketing provided additional information.…”